Jeff
Brinker, study leader and a researcher at Sandia National Laboratories as well
as a professor at the University of New Mexico, and Carlee Ashley, a Harry S.
Truman post-doctoral fellow at Sandia National Laboratories California, have
developed silica
nanoparticles that contain honeycomb cavities to store different kinds
of cancer-killing drugs.
Drug
delivery systems have become an important part of cancer research, as
researchers are looking for a replacement for chemotherapy. Traditional cancer
drugs produce negative side effects because they are released into the system
to attack cancer cells, but end up attacking healthy cells as well since they
have no direction. With drug delivery systems, such as the remote-controlled
microcarrier drug delivery system developed by Canadian researchers
and the synthetic nanopolymer
coated with cancer drugs created by Purdue researchers, scientists are
coming closer to finding methods of drug delivery with no side effects.
Now,
Brinker and Ashley have found a new technique that utilizes silica
nanoparticles that are 150 nanometers in diameter. The nanoparticles are
honeycombed with little compartments that are meant to carry various kinds of
cancer drugs directly to cancerous tissue without harming surrounding healthy
tissue.
The new
system is different from others because it utilizes protocells instead of
liposomes alone. Protocells are the combination of the nanoparticles and
membranes formed from liposomes, where the aggressive cancer drugs are sealed
tight. SiRNA, which silences the expressions of proteins to cause cell death,
is also within the honeycomb to be released. The membrane is modified with
peptides that are designed to bind to receptors overexpressed on a cancer
cell's surface. The drugs are then released from the honeycomb compartments into the cancerous
cells.
Researchers
tested the new system by exposing various phages, or viruses that attack
bacteria, to two groups of cells - one that is cancerous, and one that is
not.
"Proteins
modified with a targeting peptide that binds to a particular carcinoma exhibit
a 10,000-fold greater affinity for that cancer than for other unrelated
cells," said Ashley.
Brinker
and Ashley noted that their honeycombed protocell technique had greater
stability, targeting efficacy and cargo capacity than targeted liposomes alone.
It also had greater cytotoxicity for cell destruction of human liver cancer
cells.
In
addition, this new technique is easier to use than targeted liposomes because liposome
carriers require specialized loading strategies while the new system simply
soaks nanoparticles in different drug combinations to make personalized
medications. The lipids then protect the harmful drugs from leaking as they
travel through the human system. These nanoparticles can circulate in the
system for days or weeks depending on their size, which is engineered from 50
to 150 nanometers in diameter using an aerosolized precursor solution.
Evaporation-induced self-assembly then produces the particles, which are later
made into protocells.
"Their
overall dimensions determine how widely they'll be distributed in the
bloodstream," said Brinker. "We're altering our synthesis to favor
the smaller sizes."
The
smaller sizes are capable of navigating "under the radar" of organs
like the liver, meaning they can circulate longer.
Researchers
believe this method will be available for use in five years.
"The
enormous capacity of the nanoporous core, with its high surface area, combined
with the improved targeting of an encapsulating lipid bilayer (called a
liposome) permit a single protocell loaded with a drug cocktail to kill a
drug-resistant cancer cell," said Brinker. "That's a millionfold
increase in efficiency over comparable methods employing liposomes alone -
without nanoparticles - as drug carriers."
This study was published in Nature
Materials.